a randomized controlled study of high-dose cyclophosphamide induction therapy in adult patients with hlh

Conditions: Hemophagocytic Syndrome

Summary: adult secondary hlh involves tumors, autoimmune diseases and other causes in addition to infection,infectious factors, theoretically need different treatment methods for different etiology. but adult hlh itself disease .the situation progresses ferociously, which can cause organ damage and blood coagulation disorder and endanger life quickly, with early mortality (30days).it can be more than 50%. on the other hand, although diagnostic techniques have improved significantly, identifying the cause is still costly time, such as 1-2 weeks for the pathological diagnosis of lymphoma, leads to more patients losing further treatment due to early death. the opportunity to heal. therefore, it is important to explore effective induction therapy for adult hlh. in the majority ,early (30-day) mortality was as high as 40% after cardiac induction using hlh2004 or chop(cyclophosphamide, hydroxydaunomycin, oncovin, and prednisone) induction. hlh, on the other hand, usually requires prompt treatment before the cause is established. due to a specific infection hlh can benefit from anti-infective therapy. therefore, it is necessary to explore more effective induction therapy for adult non-infective hlh.it has very important clinical significance. adult secondary hlh has the common features of a large number of t cell proliferation and activation and a significant reduction of nk(natural killer) cells, in which the central link(natural killer) is a large number of t cells proliferation and secomplete remission etion of cytokines, which can be used as induction therapy.common target is also the pathological basis for designing unified induction scheme. cyclophosphamide is a commonly used alkylated chemotherapy drug,it's also an important immunosuppressant. based on the treatment of regenerative disorders anemia, allogeneic hematopoietic stem cell transplantation prevention.experience with plant versus host disease (gvhd) has shown that the use of cyclophosphamide exceeds a total dose of 25mg/day,two days can effectively kill cd8(cluster of differentiation 8 )+ or cd4(cluster of differentiation 4 )+t cells, and the maximum tolerated dose of this drug in humans exceeds 50mg/kg/day for two days. aiming at the central link(natural killer) of adult hlh pathogenesis, the investigators designed for the first time to use a large dose of cyclophosphamide (25mg-50mg/kg/day 2days) to inhibit the activation of t cells, inhibit the production of cytokines and block the development mechanism of hlh. this study intends to conduct a randomized controlled study, with hlh2004 scheme as the control, and the observation is large efficacy and safety of dose cyclophosphamide in induction therapy of non-infective adult hlh in order to complete remission eate a new induction treatment plan.


Eligibility criteria:
inclusion criteria: 1. age range from 18 to 65 years old (including the critical value), gender is not limited; 2. according to the diagnostic criteria of hlh-2004, hlh can be diagnosed if any of the following two criteria are met: 1. molecular diagnosis is consistent with hlh: currently known hlh related pathogenic genes exist, such as prf1, unc13d, stx11, stxbp2, rab27a, lyst, sh2d1a, birc4, itk, ap3β1, magt1, cd27 (cluster of differentiation antigen 27 )and other pathological mutations. 2. meet 5 or more of the following 8 indicators: * fever: body temperature \&gt; 38.5 ℃, continuous \&gt; 7 d; ② splenomegaly; * hemocytopenia (involving two or three peripheral blood lines) : hemoglobin \&lt; 90 g/l (\&lt; 4 weeks infant, hemoglobin \&lt; 100 g/l), platelet \&lt; 100×109/l, neutrophils \&lt; 1.0×109/l and not caused by reduced hematopoietic function of bone marrow; ④ high triglyceride (tg) sepsis and/or low fibrinogenemia: triglyceride \&gt; 3 mmol/l or 3 standard deviations above the same age, fibrinogen \&lt; 1.5g /l or less than 3 standard deviations for the same age; (5) hematophagy was found in bone marrow, spleen, liver or lymph nodes; * the activity of nk cells is decreased or absent; ⑦ serum ferritin increase: ferritin ≥500 μg/l; elevated scd25 (soluble interleukin-2 receptor). (3) those who can understand the research content, agree to comply with the research plan, and voluntarily sign the informed consent. exclusion criteria: 1. hlh caused by treatable infectious causes (such as bacteria, fungi, viruses (except epstein-barr virus), protozoa, etc.); 2. have a history of allergy or contraindications to the drugs involved in the program; 3. organ damage caused by long-term chronic diseases; 4. extreme physical weakness, unstable vital signs and inability to tolerate large doses of cyclophosphamide; 5. severe and/or uncontrolled co-morbidivities (e.g., uncontrolled diabetes, pulmonary hypertension, etc.) that the investigator believes may pose an unacceptable safety risk or interfere with protocol compliance; 6. mental instability or history of severe mental illness 7. other factors determined by the researcher that subjects are not suitable to participate in this study.

Keywords: hemophagocytic syndrome（hlh）